A Modern View of the Interstitial Space in Health and Disease

Abstract

Increases in the volume of the interstitial space are readily recognized clinically as interstitial edema formation in the loose connective tissue of skin, mucosa, and lung. However, the contents and the hydrostatic pressure of this interstitial fluid can be very difficult to determine even in experimental settings. These difficulties have long obscured what we are beginning to appreciate is a dynamic milieu that is subject to both intrinsic and extrinsic regulation. This review examines current concepts regarding regulation of interstitial volume, pressure, and flow and utilizes that background to address three major topics of interest that impact IV fluid administration. The first of these started with the discovery that excess dietary salt can be stored non-osmotically in the interstitial space with minimal impact on vascular volume and pressures. This led to the hypothesis that, along with the kidney, the interstitial space plays an active role in the long-term regulation of blood pressure. Second, it now appears that hypovolemic shock leads to systemic inflammatory response syndrome principally through the entry of digestive enzymes into the intestinal interstitial space and the subsequent progression of enzymes and inflammatory agents through the mesenteric lymphatic system to the general circulation. Lastly, current evidence strongly supports the non-intuitive view that the primary factor leading to inflammatory edema formation is a decrease in interstitial hydrostatic pressure that dramatically increases microvascular filtration.

Pulmonary hypertension in interstitial lung disease: screening, diagnosis and treatment

“…Less well appreciated is the dynamic nature of the interstitium which is characterized by the regular turnover of fluids, matrix molecules and cells. This feature impacts not only normal repair processes, but also disease manifestations [1 ▪ ].…”

The effects of gravity and compression on interstitial fluid transport in the lower limb

“…Interstitial fluid pressure can be reduced by lowering the capillary blood pressure via thermoregulatory vasoconstriction or decreasing the permeability of the capillary walls as it might be with reduced inflammation 96 . Another possible softening mechanism that is little explored is a reduction in fibroblast tensioning within the tissue which may alter the pressure–volume relationship 97 . Offsetting these favorable effects are the possible deductions in lymphatic pumping 98 , increases in fluid viscosity and higher stiffness of the solid phase 99 , all of which tend to increase, rather decrease, the apparent stiffness of the tissue when cooled.…”

3D-Printed Microarray Patches for Transdermal Applications

“…Due to the frequent filtration of ISF from surrounding lymphatic and blood vasculature, the composition of ISF is representative of metabolites that are in circulation. 9 These properties of the ID space are advantageous in two key use cases of transdermal access: drug delivery into the ID space for therapeutic applications and ISF sampling from the ID space for diagnostic or health monitoring applications.…”

“…As a result, it is critical in regulating osmotic balance and is also composed of relevant metabolites and electrolytes that are necessary for maintaining homeostasis. Due to the frequent filtration of ISF from surrounding lymphatic and blood vasculature, the composition of ISF is representative of metabolites that are in circulation …”